N-nitroso compounds, particularly alkyl nitrosoamines have been identified as carcinogens for a wide range of mamalian species. Nitrosoamines have been detected in many kinds of products such as pharmaceuticals, pesticides, cutting oils, cigarette smoke and foods like cheese, fish spices, etc.
Several classes of herbicides are known to contain small amounts of nitrosoamine impurities. Thus, for example, substituted dinitroaniline derivatives and dimethylamine salts of phenoxyalkanoic acid are major herbicides affected by this problem.
In the case of dinitroaniline derivatives, nitrosoamines are believed to be formed by the reaction of the residual nitrosating agents left over from the nitration step with the amine used in the subsequent ammination step.
For example, in the case of the typical dinitroaniline herbicide, trifluralin, the sequence of preparation is as follows: ##STR3##
From the reaction (a), small amounts of nitrosating agents are carried along with the 4-chloro-3,5-dinitro benzotrifluoride intermediate (2) for further amination (b). These nitrosating agents, believed to be nitrogen oxides, react with the amine to form nitrosamines as in equation (c). ##STR4## For a number of years now, pesticide manufacturers have been trying to reduce as much as possible the nitrosoamine impurities in their products. Originally, trifluralin, for example, contained from between 2 to 115 ppm nitrosoamine, but because of the carcinogenic problem, the Environmental Protection Agency (EPA) in the U.S.A. limited the allowable concentration of nitrosoamine to be 1 ppm. Most recently, this limit was reduced even further to 0.5 ppm.
This, of course, put a great burden upon dinitroaniline producers to find ways of avoiding or eliminating such trace impurities in their products.
Another problem which came to light concerning dinitroaniline herbicides such as trifluralin was that the product which immediately after manufacture complied with the EPA requirement, was found to have an increased nitrosoamine content, as much as tenfold, when stored for long periods of time such as during overseas shipping, or when formulated into agriculturally useful formulations. It is believed that prolonged storage and particularly subjecting the dinitroaniline to melting temperatures, as during the formulation process, causes formation of small amounts of nitrosamines.
The problem of complying with the EPA nitrosoamine standard has thus become twofold. First of all, to reduce the concentration to less than 0.5 ppm and secondly to prevent formation of the nitrosoamine with time or with further processing.
Basically there exist two approaches for reducing nitrosoamine content. One method is to eliminate or deactivate the nitrosating agent before it can react with any amine. This approach was taken by U.S. Pat. No. 4,120,905, which discloses the entraining of nitrosating agents from 4-chloro-3,5-dinitro benzo-trifluoride with a gas. Similarly, German Offenlegungsschrift No. 2,926,946 discloses purification of the dinitro benzene intermediate from nitrosating agents by crystallization. U.S. Pat. No. 4,331,468 teaches the prevention of nitrosoamine formation by the addition of monoalkanolamine retarding agent.
Another method for overcoming the nitrosoamine problem is to decompose the already formed nitrosoamines into harmless products. This method is applied by U.S. Pat. No. 4,127,610 by treating the dinitroaniline containing the nitrosamine impurity with bromine, chlorine or other selected brominating or chlorinating compounds. This patent, however, warns against prolonged contact between reactants which may result in further nitrosoamine formation rather than decomposition.
In a similar manner, U.S. Pat. No. 4,226,789 discloses the reduction of nitrosoamine content in dinitroanilines by heating the latter with either concentrated hydrochloric acid or HCl gas. This process does not entirely eliminate the nitrosoamine content and is prone to the generation of more nitrosoamines upon prolonged standing or heating. This process, furthermore, requires substantial quantities of HCl with comcomitant additional work up.